U.S. patent application number 16/053893 was filed with the patent office on 2018-12-06 for oral care compositions and methods of use.
This patent application is currently assigned to Colgate-Palmolive Company. The applicant listed for this patent is Colgate-Palmolive Company. Invention is credited to Julia Dreifus, Lisa Manus.
Application Number | 20180344596 16/053893 |
Document ID | / |
Family ID | 58544853 |
Filed Date | 2018-12-06 |
United States Patent
Application |
20180344596 |
Kind Code |
A1 |
Manus; Lisa ; et
al. |
December 6, 2018 |
Oral Care Compositions and Methods of Use
Abstract
This invention relates to oral care compositions comprising
arginine, zinc citrate and zinc oxide, and an orally acceptable
carrier, as well as to methods of using and of making these
compositions.
Inventors: |
Manus; Lisa; (Lawrenceville,
NJ) ; Dreifus; Julia; (Millstone, NJ) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Colgate-Palmolive Company |
New York |
NY |
US |
|
|
Assignee: |
Colgate-Palmolive Company
New York
NY
|
Family ID: |
58544853 |
Appl. No.: |
16/053893 |
Filed: |
August 3, 2018 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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15386031 |
Dec 21, 2016 |
10058493 |
|
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16053893 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/21 20130101; G01N
33/50 20130101; A61K 8/8164 20130101; A61K 8/362 20130101; A61K
8/88 20130101; Y10S 514/901 20130101; A61K 8/8152 20130101; A61K
8/44 20130101; A61K 8/70 20130101; A61Q 11/00 20130101; A61K 8/27
20130101 |
International
Class: |
A61K 8/27 20060101
A61K008/27; A61K 8/88 20060101 A61K008/88; A61K 8/21 20060101
A61K008/21; A61K 8/362 20060101 A61K008/362; A61K 8/44 20060101
A61K008/44; A61K 8/70 20060101 A61K008/70; A61Q 11/00 20060101
A61Q011/00; G01N 33/50 20060101 G01N033/50 |
Claims
1. An oral care buffering composition comprising: a) a basic amino
acid in free or salt form wherein the amino acid is arginine; b)
zinc oxide and zinc citrate; and c) an orally acceptable carrier,
wherein the oral care composition provides a buffering effect
against acidic conditions in the oral cavity following acid
challenge or sucrose challenge, wherein the buffering effect is
greater than a corresponding buffering effect of compositions
comprising arginine, zinc oxide or zinc citrate alone.
2. The oral care composition of claim 1, wherein the composition
maintains a pH over 5.0 when challenged in an acidic aqueous
solution with a cola beverage in an amount of about 90% v/v based
on the total volume of the solution.
3. The oral care composition of claim 1, wherein the composition
maintains a pH over 3.9 when challenged in an acidic aqueous
solution with a cola beverage in an amount of about 90% v/v based
on the total volume of the solution.
4. The oral care composition of claim 1, wherein the composition
maintains a pH over 3.0 when challenged in an acidic aqueous
solution with a cola beverage in an amount of about 90% v/v based
on the total volume of the solution.
5. The oral care composition of claim 1, wherein the composition
maintains a pH over 5.5 when challenged in an acidic aqueous
solution with a cola beverage in an amount of about 80% v/v based
on the total volume of the solution.
6. The oral care composition of claim 1, wherein the composition
maintains a pH over 4.0 when challenged in an acidic aqueous
solution with orange juice in an amount of about 55% v/v based on
the total volume of the solution.
7. The oral care composition of claim 1, wherein the composition
maintains a pH over 6.0 when challenged in an acidic aqueous
solution with orange juice in an amount of about 33% v/v based on
the total volume of the solution.
8. The oral care composition of claim 1, wherein the composition
maintains a pH over 5.0 when challenged in an acidic aqueous
solution with orange juice in an amount of about 33% v/v based on
the total volume of the solution.
9. The oral care composition of claim 1, wherein the composition
maintains a pH over 7.0 when challenged in an acidic aqueous
solution with 0.01M aqueous HCl in an amount of about 60% v/v based
on the total volume of the solution.
10. The oral care composition of claim 1, wherein the composition
maintains a pH over 8.0 when challenged in an acidic aqueous
solution with 0.01M aqueous HCl in an amount of about 60% v/v based
on the total volume of the solution.
11. The oral care composition of claim 1, wherein the composition
maintains a pH over 7.0 6 hours after sucrose challenge.
12. The oral care composition of claim 1, wherein the composition
maintains a pH over 8.0 6 hours after sucrose challenge.
13. The oral care composition of claim 1, wherein the composition
maintains a pH over 9.0 6 hours after sucrose challenge.
14. The oral care composition of claim 1, wherein the composition
maintains a pH over 7.0 24 hours after sucrose challenge.
15. The oral care composition of claim 1, wherein the composition
maintains a pH over 8.0 24 hours after sucrose challenge.
16. The oral care composition of claim 1, wherein the composition
maintains a pH over 9.0 24 hours after sucrose challenge.
17. The oral care composition of claim 1, wherein the arginine has
the L-configuration.
18. The oral care composition of claim 1 wherein the amino acid is
arginine from about 1.5 wt. %.
19. The oral care composition of claim 1, wherein the zinc citrate
is in an amount of about 0.5 wt % and zinc is present in an amount
of about 1.0% based on the weight of the oral care composition.
20. A method to identify candidate oral care buffering agents,
compositions, solutions or systems useful to mitigate acidic
conditions in the oral cavity comprising the steps of providing a
first sample and a second sample selected from enamel from a human
or bovine source; contacting the first sample with a measured
quantity of acidic substance; contacting the first sample with a
candidate oral care buffering agent, composition, solution or
system; determining whether acid erosion has occurred to the first
sample; contacting the second sample with the measured quantity of
acidic substance; contacting the second sample with any of
Composition 1, et seq.; determining whether acid erosion has
occurred to the second sample, wherein acid erosion of the first
sample being less than or equal to that of the second sample
indicates that the candidate oral care buffering agents,
compositions, solutions or systems can be useful to mitigate acidic
conditions in the oral cavity.
21. A method to identify candidate oral care buffering agents,
compositions, solutions or systems useful to mitigate acidic
conditions in the oral cavity comprising the steps of providing a
first sample and a second sample selected from enamel from a human
or bovine source; contacting the first sample with a measured
quantity of acidic substance; contacting the first sample with a
candidate oral care buffering agent, composition, solution or
system; determining whether acid erosion has occurred to the first
sample; contacting the second sample with the measured quantity of
acidic substance; contacting the second sample with any of
Composition 1, et seq.; determining whether acid erosion has
occurred to the second sample, wherein acid erosion of the first
sample being less than or equal to that of the second sample
indicates that the candidate oral care buffering agents,
compositions, solutions or systems can be useful to mitigate acidic
conditions in the oral cavity.
22. A method to identify candidate oral care buffering agents,
compositions, solutions or systems useful to mitigate acidic
conditions in the oral cavity comprising the steps of providing a
first sample and a second sample selected from saliva, wherein the
first and second samples have the same initial pH; contacting the
first sample with a measured quantity of a sugar to form a
solution; contacting the first sample with a candidate oral care
buffering agent, composition, solution or system; determining
whether the pH of the first sample solution has changed; contacting
the second sample with the measured quantity of sugar to form a
solution; contacting the second sample with any of Composition 1,
et seq.; determining whether the pH of the second sample solution
has changed, wherein an increase in pH greater in the first sample
that being greater than or equal to that of the second sample
indicates that the candidate oral care buffering agents,
compositions, solutions or systems can be useful to mitigate acidic
conditions in the oral cavity.
Description
FIELD
[0001] This invention relates to oral care compositions comprising
arginine or salt thereof, zinc oxide and zinc citrate, and an
orally acceptable carrier, as well as to methods of using and of
making these compositions.
BACKGROUND
[0002] Natural buffering capacity of human saliva is controlled
principally by the carbonic acid/bicarbonate system. Upon acid
exposure from an external source (soft drinks, fruit juices,
coffee) or internal source (stomach acid), this chemical system
aids in neutralizing saliva toward higher pH values, which protects
enamel. Poor saliva buffering capacity can cause poor oral health
including increased risk for enamel erosion, caries, and high
levels of oral bacteria. Arginine and other basic amino acids have
been proposed for use in oral care and are believed to have
significant benefits in combating cavity formation and tooth
sensitivity. Commercially available arginine-based toothpaste
contains arginine bicarbonate and precipitated calcium carbonate,
but not fluoride. The carbonate ion is believed to have cariostatic
properties, and the calcium is believed to form in complex with
arginine to provide a protective effect.
[0003] However, the formulation of certain oral care compositions
presents special challenges. For example, not all preservatives are
active at higher pH. Some preservatives negatively affect the taste
or aesthetics of the product. While certain preservatives, such as
ethanol or parabens, are known to be effective at a range of pHs,
these preservatives are not suitable for all products or all
markets.
[0004] Zinc formulations also present challenges. Zinc is a
well-known antimicrobial agent used in toothpaste compositions.
Zinc is also a well-known essential mineral for human health, and
has been reported to help strengthen dental enamel and to promote
cell repair. Unfortunately, conventional toothpaste formulations
often require a high concentrations of zinc, e.g., 2% by weight or
more, to achieve efficacy. At this concentration, the zinc imparts
a notably astringent taste to the composition.
[0005] Accordingly, there is a need for improved oral care
compositions that promote rapid and/or sustained buffering capacity
of saliva.
BRIEF SUMMARY
[0006] It has been found that the combination of a basic amino acid
(i.e., arginine) and one or more sources of zinc (i.e., zinc oxide
and zinc citrate, e.g., zinc citrate trihydrate) provides
surprisingly effective buffering effects to counteract acidic
conditions in the oral cavity.
[0007] Therefore, in one aspect, disclosed is an oral care
composition (Composition 1.0) comprising: [0008] a. Basic amino
acid in free or salt form, wherein the basic amino acid is arginine
(e.g., free form arginine); [0009] b. zinc oxide and zinc citrate;
and [0010] c. an orally acceptable carrier. For example, the
invention contemplates any of the following compositions (unless
otherwise indicated, values are given as percentage of the overall
weight of the composition) [0011] 1.1 Composition 1, wherein the
composition maintains a pH over 5.0 (e.g., about 5.2) when
challenged in an acidic aqueous solution with a cola beverage in an
amount of about 90% v/v (e.g., about 91%) based on the total volume
of the solution. [0012] 1.2 Composition 1 or 1.1, wherein the
composition maintains a pH over 3.9 (e.g., about 3.92 or 4.0) when
challenged in an acidic aqueous solution with a cola beverage in an
amount of about 90% v/v (e.g., about 91%) based on the total volume
of the solution. [0013] 1.3 Any of the preceding compositions,
wherein the composition maintains a pH over 3.0 (e.g., about 3.3)
when challenged in an acidic aqueous solution with a cola beverage
in an amount of about 90% v/v (e.g., about 91%) based on the total
volume of the solution. [0014] 1.4 Any of the preceding
compositions, wherein the composition maintains a pH over 5.5
(e.g., about 5.5, 5.6 or 5.7) when challenged in an acidic aqueous
solution with a cola beverage in an amount of about 80% v/v (e.g.,
about 83%) based on the total volume of the solution. [0015] 1.5
Any of the preceding compositions, wherein the composition
maintains a pH over 4.0 (e.g., about 4.2, 4.3, 4.4 or 4.5) when
challenged in an acidic aqueous solution with orange juice in an
amount of about 55% v/v (e.g., about 55.5%) based on the total
volume of the solution. [0016] 1.6 Any of the preceding
compositions, wherein the composition maintains a pH over 6.0
(e.g., about 6.1) when challenged in an acidic aqueous solution
with orange juice in an amount of about 33% v/v (e.g., about 33.3%)
based on the total volume of the solution. [0017] 1.7 Any of the
preceding compositions, wherein the composition maintains a pH over
5.0 (e.g., about 5.1 or 5.6) when challenged in an acidic aqueous
solution with orange juice in an amount of about 33% v/v (e.g.,
about 33.3%) based on the total volume of the solution. [0018] 1.8
Any of the preceding compositions, wherein the composition
maintains a pH over 7.0 (e.g., about 7.1, 7.2, 7.3, 7.4, 7.5, 7.6,
7.7, 7.8 or 7.9) when challenged in an acidic aqueous solution with
0.01M HCl in an amount of about 60% v/v based on the total volume
of the solution. [0019] 1.9 Any of the preceding compositions,
wherein the composition maintains a pH over 8.0 (e.g., about 8.1,
8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8 or 8.9) when challenged in an
acidic aqueous solution with 0.01M HCl in an amount of about 60%
v/v based on the total volume of the solution. [0020] 1.10 Any of
the preceding compositions, wherein the composition maintains a pH
over 7.0 (e.g., about 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8 or
7.9) 6 hours after sucrose challenge. [0021] 1.11 Any of the
preceding compositions, wherein the composition maintains a pH over
8.0 (e.g., about 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8 or 8.9) 6
hours after sucrose challenge. [0022] 1.12 Any of the preceding
compositions, wherein the composition maintains a pH over 9.0
(e.g., about 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8 or 9.9) 6 hours
after sucrose challenge. [0023] 1.13 Any of the preceding
compositions, wherein the composition maintains a pH over 7.0
(e.g., about 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8 or 7.9) 24
hours after sucrose challenge. [0024] 1.14 Any of the preceding
compositions, wherein the composition maintains a pH over 8.0
(e.g., about 8.1, 8.2, 8.3, 8.4, 8.5, 8.6, 8.7, 8.8 or 8.9) 24
hours after sucrose challenge. [0025] 1.15 Any of the preceding
compositions, wherein the composition maintains a pH over 9.0
(e.g., about 9.1, 9.2, 9.3, 9.4, 9.5, 9.6, 9.7, 9.8 or 9.9) 24
hours after sucrose challenge. [0026] 1.16 Composition 1.0 wherein
the basic amino acid has the L-configuration (e.g., L-arginine).
[0027] 1.17 Any of the preceding compositions wherein the arginine
is in free form. [0028] 1.18 Any of the preceding compositions
wherein the basic amino acid is provided in the form of a di- or
tri-peptide comprising arginine, or salts thereof. [0029] 1.19 Any
of the preceding compositions wherein the arginine is present in an
amount corresponding to 1% to 15%, e.g., 3 wt. % to 10 wt. % of the
total composition weight, about e.g., 1.5%, 4%, 5%, or 8%, wherein
the weight of the basic amino acid is calculated as free form.
[0030] 1.20 Any of the preceding compositions wherein the arginine
is present in an amount from 0.1 wt. %-6.0 wt. %. (e.g., about 1.5
wt %). [0031] 1.21 Any of the preceding compositions wherein the
arginine is present in an amount of about 1.5 wt. %. [0032] 1.22
Any of the preceding compositions wherein the amino acid is
L-arginine. [0033] 1.23 Any of the preceding compositions wherein
the amino acid is free form arginine. [0034] 1.24 Any of the
preceding compositions wherein the amino acid is arginine
phosphate. [0035] 1.25 Any of the preceding compositions wherein
the amino acid is arginine hydrochloride. [0036] 1.26 Any of the
preceding compositions wherein the amino acid is arginine
bicarbonate. [0037] 1.27 Any of the preceding compositions wherein
the amino acid is arginine ionized by neutralization with an acid
or a salt of an acid. [0038] 1.28 Any of preceding compositions
wherein the composition is ethanol-free. [0039] 1.29 Any of the
preceding compositions further comprising a fluoride source
selected from: stannous fluoride, sodium fluoride, potassium
fluoride, sodium monofluorophosphate, sodium fluorosilicate,
ammonium fluorosilicate, amine fluoride (e.g.,
N'-octadecyltrimethylendiamine-N,N,N'-tris(2-ethanol)-dihydrofluoride),
ammonium fluoride, titanium fluoride, hexafluorosulfate, and
combinations thereof [0040] 1.30 Any of the preceding compositions
wherein the fluoride source is sodium fluoride. [0041] 1.31 Any of
the preceding compositions wherein the fluoride source is a
fluoride salt present in an amount of 0.1 wt. % to 2 wt. % (0.1 wt
%-0.6 wt. %) of the total composition weight (e.g., sodium fluoride
(e.g., about 0.32 wt. %). [0042] 1.32 Any of the preceding
compositions wherein the fluoride source is a soluble fluoride salt
which provides fluoride ion in an amount of from 50 to 25,000 ppm
(e.g., 750-2000 ppm, e.g., 1000-1500 ppm, e.g., about 1000 ppm,
e.g., about 1450 ppm) [0043] 1.33 Any of the preceding compositions
wherein the fluoride source is sodium fluoride which provides
fluoride in an amount from 750-2000 ppm (e.g., about 1450 ppm)
[0044] 1.34 Any of the preceding compositions wherein the fluoride
source is sodium fluoride and which provides fluoride in an amount
from 1000 ppm-1500 ppm. [0045] 1.35 Any of the preceding
compositions wherein the fluoride source is sodium fluoride and
which provides fluoride in an amount of about 1450 ppm. [0046] 1.36
Any of the preceding compositions wherein the pH is between 7.5 and
10.5, e.g., 8-9.5, e.g., 7.2-9.0, about 8.0, about 9.0. [0047] 1.37
Any of the preceding compositions further comprising calcium
carbonate and/or precipitated calcium carbonate. [0048] 1.38 Any of
the preceding compositions further comprising an effective amount
of one or more alkali phosphate salts, e.g., sodium, potassium or
calcium salts, e.g., selected from alkali dibasic phosphate and
alkali pyrophosphate salts, e.g., alkali phosphate salts selected
from sodium phosphate dibasic, potassium phosphate dibasic,
dicalcium phosphate dihydrate, calcium pyrophosphate, tetrasodium
pyrophosphate, tetrapotassium pyrophosphate, sodium
tripolyphosphate, disodium hydrogenorthophoshpate, monosodium
phosphate, pentapotassium triphosphate and mixtures of any of two
or more of these, e.g., in an amount of 0.1-20%, e.g., 0.1-8%,
e.g., e.g., 0.2 to 5%, e.g., 0.3 to 2%, e.g., 0.3 to 1%, e.g about
0.5%, about 1%, about 2%, about 5%, about 6%, by weight of the
composition. [0049] 1.39 Any of the preceding compositions
comprising tetrapotassium pyrophosphate, disodium
hydrogenorthophoshpate, monosodium phosphate, and pentapotassium
triphosphate. [0050] 1.40 Any of the preceding compositions
comprising a polyphosphate. [0051] 1.41 The composition of 1.40,
wherein the polyphosphate is tetrasodium pyrophosphate. [0052] 1.42
The composition of 1.42, wherein the tetrasodium pyrophosphate is
from 0.1-1.0 wt % (e.g., about 0.5 wt %). [0053] 1.43 Any of the
preceding compositions further comprising an abrasive or
particulate (e.g., silica). [0054] 1.44 Any of the preceding
compositions wherein the silica is synthetic amorphous silica
(e.g., 1%-28% by wt.) (e.g., 8%-25% by wt.). [0055] 1.45 Any of the
preceding composition wherein the silica abrasives are silica gels
or precipitated amorphous silicas, e.g. silicas having an average
particle size ranging from 2.5 microns to 12 microns. [0056] 1.46
Any of the preceding compositions further comprising a small
particle silica having a median particle size (d50) of 1-5 microns
(e.g., 3-4 microns) (e.g., about 5 wt. % Sorbosil AC43 from PQ
Corporation, Warrington, United Kingdom). [0057] 1.47 Any of the
preceding compositions wherein 20-30 wt % of the total silica in
the composition is small particle silica (e.g., having a median
particle size (d50) of 3-4 microns) and wherein the small particle
silica is about 5 wt. % of the oral care composition. [0058] 1.48
Any of the preceding compositions comprising silica wherein the
silica is used as a thickening agent, e.g., particle silica. [0059]
1.49 Any of the preceding compositions further comprising a
nonionic surfactant, wherein the nonionic surfactant is in an
amount of from 0.5-5%, e.g, 1-2%, selected from poloxamers (e.g.,
poloxamer 407), polysorbates (e.g., polysorbate 20), polyoxyl
hydrogenated castor oil (e.g., polyoxyl 40 hydrogenated castor
oil), and mixtures thereof. [0060] 1.50 Composition 1.50, wherein
the poloxamer nonionic surfactant has a polyoxypropylene molecular
mass of from 3000 to 5000 g/mol and a polyoxyethylene content of
from 60 to 80 mol %, e.g., the poloxamer nonionic surfactant
comprises poloxamer 407. [0061] 1.51 Any of the preceding
compositions, wherein the ratio of the amount of zinc oxide (e.g.,
wt. %) to zinc citrate (e.g., wt %) is from 1.5:1 to 4.5:1 (e.g.,
2:1, 2.5:1, 3:1, 3.5:1, or 4:1). [0062] 1.52 Any of the preceding
compositions, wherein the zinc citrate is in an amount of from 0.25
to 1.0 wt % (e.g., 0.5 wt. %) and zinc oxide may be present in an
amount of from 0.75 to 1.25 wt % (e.g., 1.0 wt. %) based on the
weight of the oral care composition. [0063] 1.53 Any of the
preceding compositions wherein the zinc citrate is about 0.5 wt %.
[0064] 1.54 Any of the preceding compositions wherein the zinc
oxide is about 1.0 wt %. [0065] 1.55 Any of the preceding
compositions where the zinc citrate is about 0.5 wt % and the zinc
oxide is about 1.0 wt %. [0066] 1.56 Any of the preceding
compositions wherein the benzyl alcohol is present from 0.1-0.6 wt
%., (e.g., 0.1-0.4 wt %) e.g. about 0.1 wt. %, about 0.2 wt. %, or
about 0.3 wt. %. [0067] 1.57 Any of the preceding compositions
wherein the benzyl alcohol is about 0.1 wt %. [0068] 1.58 Any of
the preceding composition wherein benzyl alcohol is present at is
considered a preservative. [0069] 1.59 Any of the preceding
compositions comprising polymer films. [0070] 1.60 Any of the
preceding compositions comprising flavoring, fragrance and/or
coloring agent. [0071] 1.61 The composition of 1.61, wherein the
flavoring agent is sodium saccharin, sucralose, or a mixture
thereof [0072] 1.62 Any of the preceding compositions, wherein the
composition comprises a thickening agent selected from the group
consisting of carboxyvinyl polymers, carrageenan, xanthan,
hydroxyethyl cellulose and water soluble salts of cellulose ethers
(e.g., sodium carboxymethyl cellulose and sodium carboxymethyl
hydroxyethyl cellulose). [0073] 1.63 Any of the preceding
compositions, wherein the composition comprises sodium
carboxymethyl cellulose (e.g., from 0.5 wt. %-1.5 wt. %). [0074]
1.64 Any of the preceding compositions comprising from 5%-40%,
e.g., 10%-35%, e.g., about 15%, 25%, 30%, and 35% water. [0075]
1.65 Any of the preceding compositions comprising an additional
antibacterial agent selected from halogenated diphenyl ether (e.g.
triclosan), herbal extracts and essential oils (e.g., rosemary
extract, tea extract, magnolia extract, thymol, menthol,
eucalyptol, geraniol, carvacrol, citral, hinokitol, catechol,
methyl salicylate, epigallocatechin gallate, epigallocatechin,
gallic acid, miswak extract, sea-buckthorn extract), bisguanide
antiseptics (e.g., chlorhexidine, alexidine or octenidine),
quaternary ammonium compounds (e.g., cetylpyridinium chloride
(CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC),
N-tetradecyl-4-ethylpyridinium chloride (TDEPC)), phenolic
antiseptics, hexetidine, octenidine, sanguinarine, povidone iodine,
delmopinol, salifluor, metal ions (e.g., zinc salts, for example,
Zinc Chloride, Zinc Lactate, Zinc Sulfate, stannous salts, copper
salts, iron salts), sanguinarine, propolis and oxygenating agents
(e.g., hydrogen peroxide, buffered sodium peroxyborate or
peroxycarbonate), phthalic acid and its salts, monoperthalic acid
and its salts and esters, ascorbyl stearate, oleoyl sarcosine,
alkyl sulfate, dioctyl sulfosuccinate, salicylanilide, domiphen
bromide, delmopinol, octapinol and other piperidino derivatives,
nicin preparations, chlorite salts; and mixtures of any of the
foregoing. [0076] 1.66 Any of the preceding compositions comprising
an antioxidant, e.g., selected from the group consisting of
Co-enzyme Q10, PQQ, Vitamin C, Vitamin E, Vitamin A, BHT,
anethole-dithiothione, and mixtures thereof [0077] 1.67 Any of the
preceding compositions comprising a whitening agent. [0078] 1.68
Any of the preceding compositions comprising a whitening agent
selected from a whitening active selected from the group consisting
of peroxides, metal chlorites, perborates, percarbonates,
peroxyacids, hypochlorites, and combinations thereof. [0079] 1.69
Any of the preceding compositions further comprising hydrogen
peroxide or a hydrogen peroxide source, e.g., urea peroxide or a
peroxide salt or complex (e.g., such as peroxyphosphate,
peroxycarbonate, perborate, peroxysilicate, or persulphate salts;
for example calcium peroxyphosphate, sodium perborate, sodium
carbonate peroxide, sodium peroxyphosphate, and potassium
persulfate), or hydrogen peroxide polymer complexes such as
hydrogen peroxide-polyvinyl pyrrolidone polymer complexes. [0080]
1.70 Any of the preceding compositions, wherein the glycerin is in
an amount from 20%-40% by wt. of the composition. [0081] 1.71 Any
of the preceding compositions, wherein the composition further
comprises sorbitol.
[0082] 1.72 The composition of 1.72, wherein the sorbitol is from
10%-20% by wt. of the composition. [0083] 1.73 Any of the preceding
compositions further comprising an agent that interferes with or
prevents bacterial attachment, e.g., ethyl lauroyl argininate (ELA)
or chitosan. [0084] 1.74 Any of the preceding compositions
comprising: [0085] a. about 1.0% zinc oxide [0086] b. about 0.5%
zinc citrate [0087] c. about 1.5% L-arginine [0088] d. about 0.32%
sodium fluoride; [0089] e. about 35% glycerin; [0090] 1.75 Any of
compositions 1.0-1.81 comprising: [0091] a. about 1.0% zinc oxide
[0092] b. about 0.5% zinc citrate [0093] c. about 5% L-arginine
[0094] d. about 0.32% sodium fluoride; [0095] e. about 26%
glycerin; and [0096] f. about 13% sorbitol; [0097] 1.76 Any of the
preceding compositions effective upon application to the oral
cavity, e.g., by rinsing, optionally in conjunction with brushing,
to (i) reduce or inhibit formation of dental caries, (ii) reduce,
repair or inhibit pre-carious lesions of the enamel, e.g., as
detected by quantitative light-induced fluorescence (QLF) or
electrical caries measurement (ECM), (iii) reduce or inhibit
demineralization and promote remineralization of the teeth, (iv)
reduce hypersensitivity of the teeth, (v) reduce or inhibit
gingivitis, (vi) promote healing of sores or cuts in the mouth,
(vii) reduce levels of acid producing bacteria, (viii) to increase
relative levels of arginolytic bacteria, (ix) inhibit microbial
biofilm formation in the oral cavity, (x) raise and/or maintain
plaque pH at levels of at least pH 5.5 following sugar challenge,
(xi) reduce plaque accumulation, (xii) treat, relieve or reduce dry
mouth, (xiii) clean the teeth and oral cavity (xiv) reduce erosion,
(xv) prevents stains and/or whiten teeth, (xvi) immunize the teeth
against cariogenic bacteria; and/or (xvii) promote systemic health,
including cardiovascular health, e.g., by reducing potential for
systemic infection via the oral tissues. [0098] 1.77 Any of the
preceding oral compositions, wherein the oral composition may be
any of the following oral compositions selected from the group
consisting of: a toothpaste or a dentifrice, a mouthwash or a mouth
rinse, a topical oral gel, and a denture cleanser. [0099] 1.78 A
composition obtained or obtainable by combining the ingredients as
set forth in any of the preceding compositions.
[0100] A composition obtained or obtainable by combining the
ingredients as set forth in any of the preceding compositions.
[0101] A composition for use as set for in any of the preceding
compositions.
[0102] In another embodiment, the invention encompasses a method
(Method 1) to improve oral health comprising applying an effective
amount of the oral composition of any of the embodiments set forth
above to the oral cavity of a subject in need thereof, e.g., a
method to [0103] i. reduce or inhibit formation of dental caries,
[0104] ii. reduce, repair or inhibit early enamel lesions, e.g., as
detected by quantitative light-induced fluorescence (QLF) or
electrical caries measurement (ECM), [0105] iii. reduce or inhibit
demineralization and promote remineralization of the teeth, [0106]
iv. reduce hypersensitivity of the teeth, [0107] v. reduce or
inhibit gingivitis, [0108] vi. promote healing of sores or cuts in
the mouth, [0109] vii. reduce levels of acid producing bacteria,
[0110] viii. to increase relative levels of arginolytic bacteria,
[0111] ix. inhibit microbial bio film formation in the oral cavity,
[0112] x. raise and/or maintain plaque pH at levels of at least pH
5.5 following sugar challenge, [0113] xi. reduce plaque
accumulation, [0114] xii. treat dry mouth, [0115] xiii. enhance
systemic health, including cardiovascular health, e.g., by reducing
potential for systemic infection via the oral tissues, [0116] xiv.
Whiten teeth, [0117] xv. reduce erosion of the teeth, [0118] xvi.
immunize (or protect) the teeth against cariogenic bacteria and
their effects, and/or [0119] xvii. clean the teeth and oral
cavity.
[0120] In another embodiment, the invention relates to a method to
identify candidate oral care buffering agents, compositions,
solutions or systems useful to mitigate acidic conditions in the
oral cavity. (Method 2)
[0121] Therefore, method 2 includes 2.1. A ex vivo method to
identify candidate oral care buffering agents, compositions,
solutions or systems useful to mitigate acidic conditions in the
oral cavity comprising the steps of providing a first sample and a
second sample, e.g., saliva, wherein the first and second samples
have the same initial pH; contacting the first sample with a
measured quantity of acidic substance, e.g., cola, coffee, wine,
orange juice or aqueous acids (i.e., 1% HCl solution) to form a
solution; contacting the first sample with a candidate oral care
buffering agent, composition, solution or system; determining
whether the pH of the first sample solution has changed; contacting
the second sample with the measured quantity of acidic substance to
form a solution; contacting the second sample with any of
Composition 1, et seq.; determining whether the pH of the second
sample solution has changed, wherein an increase in pH greater in
the first sample being greater than or equal to that of the second
sample indicates that the candidate oral care buffering agents,
compositions, solutions or systems can be useful to mitigate acidic
conditions in the oral cavity.
[0122] 2.2 An ex vivo method to identify candidate oral care
buffering agents, compositions, solutions or systems useful to
mitigate acidic conditions in the oral cavity comprising the steps
of providing a first sample and a second sample, e.g., enamel from
a human or bovine source; contacting the first sample with a
measured quantity of acidic substance, e.g., cola, coffee, wine,
orange juice or aqueous acids (i.e., 1% HCl solution); contacting
the first sample with a candidate oral care buffering agent,
composition, solution or system; determining whether acid erosion
has occurred to the first sample; contacting the second sample with
the measured quantity of acidic substance; contacting the second
sample with any of Composition 1, et seq.; determining whether acid
erosion has occurred to the second sample, wherein acid erosion of
the first sample being less than or equal to that of the second
sample indicates that the candidate oral care buffering agents,
compositions, solutions or systems can be useful to mitigate acidic
conditions in the oral cavity.
[0123] 2.3 An ex vivo method to identify candidate oral care
buffering agents, compositions, solutions or systems useful to
mitigate acidic conditions in the oral cavity comprising the steps
of providing a first sample and a second sample, e.g., saliva,
wherein the first and second samples have the same initial pH;
contacting the first sample with a measured quantity of a sugar,
e.g., sucrose to form a solution; contacting the first sample with
a candidate oral care buffering agent, composition, solution or
system; determining whether the pH of the first sample solution has
changed; contacting the second sample with the measured quantity of
sugar to form a solution; contacting the second sample with any of
Composition 1, et seq.; determining whether the pH of the second
sample solution has changed, wherein an increase in pH greater in
the first sample that being greater than or equal to that of the
second sample indicates that the candidate oral care buffering
agents, compositions, solutions or systems can be useful to
mitigate acidic conditions in the oral cavity.
[0124] The invention further relates to a method to treat
acid-related conditions in the oral cavity, comprising
administering to a subject any of Composition 1, et seq.
BRIEF DESCRIPTION OF THE FIGURES
[0125] In part, other aspects, features, benefits and advantages of
the embodiments described herein will be apparent with regard to
the following description, appended claims and accompanying
figures.
[0126] FIG. 1 illustrates the pH of whole saliva treated with zinc
oxide/zinc citrate/arginine solutions before and after acid
challenge with a cola beverage as a function of volume of cola
added to the solution, where the solutions having varying
concentrations of zinc oxide/zinc citrate/arginine.
[0127] FIG. 2 illustrates the pH of whole saliva treated with zinc
oxide/zinc citrate/arginine solutions before and after acid
challenge with a cola beverage as a function of volume of cola
added to the solution in comparison with control solutions.
[0128] FIG. 3 illustrates the pH of whole saliva treated with zinc
oxide/zinc citrate/arginine solutions before and after acid
challenge with orange juice as a function of volume of orange juice
added to the solution, where the solutions having varying
concentrations of zinc oxide/zinc citrate/arginine.
[0129] FIG. 4 illustrates the pH of whole saliva treated with zinc
oxide/zinc citrate/arginine solutions before and after acid
challenge with orange juice as a function of volume of orange juice
added to the solution in comparison with control solutions.
[0130] FIG. 5 illustrates the pH of whole saliva from a donor
(Donor 1) treated with zinc oxide/zinc citrate/arginine solutions
after acid challenge with a dilute hydrochloric acid as a function
of reagent added to the solution in comparison with control
solutions.
[0131] FIG. 6 illustrates the pH of whole saliva from a donor
(Donor 2) treated with zinc oxide/zinc citrate/arginine solutions
after acid challenge with a dilute hydrochloric acid as a function
of reagent added to the solution in comparison with control
solutions.
[0132] FIG. 7 illustrates the pH of whole saliva from a donor
(Donor 3) treated with zinc oxide/zinc citrate/arginine solutions
after acid challenge with a dilute hydrochloric acid as a function
of reagent added to the solution in comparison with control
solutions.
[0133] FIG. 8 illustrates the pH of whole saliva from a donor
(Donor A) treated with zinc oxide/zinc citrate/arginine solutions
having various concentrations of zinc ion as a function of
time.
[0134] FIG. 9 illustrates the pH of whole saliva from a donor
(Donor B) treated with zinc oxide/zinc citrate/arginine solutions
having various concentrations of zinc ion as a function of
time.
[0135] FIG. 10 illustrates the pH of whole saliva from a donor
(Donor C) treated with zinc oxide/zinc citrate/arginine solutions
having various concentrations of zinc ion as a function of
time.
[0136] FIG. 11 illustrates the pH of whole saliva from a donor
(Donor A) treated with zinc oxide/zinc citrate/arginine solutions
after sucrose challenge as a function of time in comparison with
control solutions.
[0137] FIG. 12 illustrates the pH of whole saliva from a donor
(Donor A) treated with arginine solutions having various
concentrations of arginine after sucrose challenge as a function of
time.
[0138] FIG. 13 illustrates the pH of whole saliva from a donor
(Donor B) treated with arginine solutions having various
concentrations of arginine after sucrose challenge as a function of
time.
[0139] FIG. 14 illustrates the pH of whole saliva from a donor
(Donor C) treated with arginine solutions having various
concentrations of arginine after sucrose challenge as a function of
time.
[0140] FIG. 15 illustrates the pH of whole saliva from a donor
(Donor A) treated with zinc oxide/zinc citrate solutions having
various concentrations of zinc oxide/zinc citrate after sucrose
challenge as a function of time.
[0141] FIG. 16 illustrates the pH of whole saliva from a donor
(Donor B) treated with zinc oxide/zinc citrate solutions having
various concentrations of zinc oxide/zinc citrate after sucrose
challenge as a function of time.
[0142] FIG. 17 illustrates the pH of whole saliva from a donor
(Donor C) treated with zinc oxide/zinc citrate solutions having
various concentrations of zinc oxide/zinc citrate after sucrose
challenge as a function of time.
[0143] FIG. 18 illustrates the pH of whole saliva from a donor
(Donor A) treated with zinc oxide solutions having various
concentrations of zinc oxide after sucrose challenge as a function
of time.
[0144] FIG. 19 illustrates the pH of whole saliva from a donor
(Donor B) treated with zinc oxide solutions having various
concentrations of zinc oxide after sucrose challenge as a function
of time.
[0145] FIG. 20 illustrates the pH of whole saliva from a donor
(Donor C) treated with zinc oxide solutions having various
concentrations of zinc oxide after sucrose challenge as a function
of time.
[0146] FIG. 21 illustrates the pH of whole saliva from a donor
(Donor B) treated with zinc citrate solutions having various
concentrations of zinc citrate after sucrose challenge as a
function of time.
[0147] FIG. 22 illustrates the pH of whole saliva from a donor
(Donor B) treated with zinc citrate solutions having various
concentrations of zinc citrate after sucrose challenge as a
function of time.
[0148] FIG. 23 illustrates the pH of whole saliva from a donor
(Donor C) treated with zinc citrate solutions having various
concentrations of zinc citrate after sucrose challenge as a
function of time.
DETAILED DESCRIPTION
[0149] As used herein, the term "oral composition" means the total
composition that is delivered to the oral surfaces. The composition
is further defined as a product which, during the normal course of
usage, is not, the purposes of systemic administration of
particular therapeutic agents, intentionally swallowed but is
rather retained in the oral cavity for a time sufficient to contact
substantially all of the dental surfaces and/or oral tissues for
the purposes of oral activity. Examples of such compositions
include, but are not limited to, toothpaste or a dentifrice, a
mouthwash or a mouth rinse, a topical oral gel, a denture cleanser,
and the like.
[0150] As used herein, the term "dentifrice" means paste, gel, or
liquid formulations unless otherwise specified. The dentifrice
composition can be in any desired form such as deep striped,
surface striped, multi-layered, having the gel surrounding the
paste, or any combination thereof. Alternatively the oral
composition may be dual phase dispensed from a separated
compartment dispenser.
Basic Amino Acids
[0151] The basic amino acids which can be used in the compositions
and methods of the invention include not only naturally occurring
basic amino acids, such as arginine, lysine, and histidine, but
also any basic amino acids having a carboxyl group and an amino
group in the molecule, which are water-soluble and provide an
aqueous solution with a pH of 7 or greater.
[0152] Accordingly, basic amino acids include, but are not limited
to, arginine, lysine, serine, citrullene, ornithine, creatine,
histidine, diaminobutanoic acid, diaminoproprionic acid, salts
thereof or combinations thereof. In a particular embodiment, the
basic amino acids are selected from arginine, citrullene, and
ornithine.
[0153] In certain embodiments, the basic amino acid is arginine,
for example, L-arginine, or a salt thereof.
[0154] The compositions of the invention (e.g., Composition 1.0 et
seq) are intended for topical use in the mouth and so salts for use
in the present invention should be safe for such use, in the
amounts and concentrations provided. Suitable salts include salts
known in the art to be pharmaceutically acceptable salts are
generally considered to be physiologically acceptable in the
amounts and concentrations provided. Physiologically acceptable
salts include those derived from pharmaceutically acceptable
inorganic or organic acids or bases, for example acid addition
salts formed by acids which form a physiological acceptable anion,
e.g., hydrochloride or bromide salt, and base addition salts formed
by bases which form a physiologically acceptable cation, for
example those derived from alkali metals such as potassium and
sodium or alkaline earth metals such as calcium and magnesium.
Physiologically acceptable salts may be obtained using standard
procedures known in the art, for example, by reacting a
sufficiently basic compound such as an amine with a suitable acid
affording a physiologically acceptable anion.
Fluoride Ion Source
[0155] The oral care compositions (e.g., Composition 1.0 et seq)
may further include one or more fluoride ion sources, e.g., soluble
fluoride salts. A wide variety of fluoride ion-yielding materials
can be employed as sources of soluble fluoride in the present
compositions. Examples of suitable fluoride ion-yielding materials
are found in U.S. Pat. No. 3,535,421, to Briner et al.; U.S. Pat.
No. 4,885,155, to Parran, Jr. et al. and U.S. Pat. No. 3,678,154,
to Widder et al., each of which are incorporated herein by
reference. Representative fluoride ion sources used with the
present invention (e.g., Composition 1.0 et seq.) include, but are
not limited to, stannous fluoride, sodium fluoride, potassium
fluoride, sodium monofluorophosphate, sodium fluorosilicate,
ammonium fluorosilicate, amine fluoride, ammonium fluoride, and
combinations thereof. In certain embodiments the fluoride ion
source includes stannous fluoride, sodium fluoride, sodium
monofluorophosphate as well as mixtures thereof. Where the
formulation comprises calcium salts, the fluoride salts are
preferably salts wherein the fluoride is covalently bound to
another atom, e.g., as in sodium monofluorophosphate, rather than
merely ionically bound, e.g., as in sodium fluoride.
Surfactants
[0156] The invention may in some embodiments contain anionic
surfactants, e.g., the Compositions of Composition 1.0, et seq.,
for example, water-soluble salts of higher fatty acid monoglyceride
monosulfates, such as the sodium salt of the monosulfated
monoglyceride of hydrogenated coconut oil fatty acids such as
sodium N-methyl N-cocoyl taurate, sodium cocomo-glyceride sulfate;
higher alkyl sulfates, such as sodium lauryl sulfate; higher
alkyl-ether sulfates, e.g., of formula
CH.sub.3(CH.sub.2).sub.mCH.sub.2(OCH.sub.2CH.sub.2).sub.nOSO.sub.3X,
wherein m is 6-16, e.g., 10, n is 1-6, e.g., 2, 3 or 4, and X is Na
or, for example sodium laureth-2 sulfate
(CH.sub.3(CH2).sub.10CH.sub.2(OCH.sub.2CH.sub.2).sub.2OSO.sub.3Na);
higher alkyl aryl sulfonates such as sodium dodecyl benzene
sulfonate (sodium lauryl benzene sulfonate); higher alkyl
sulfoacetates, such as sodium lauryl sulfoacetate (dodecyl sodium
sulfoacetate), higher fatty acid esters of 1,2 dihydroxy propane
sulfonate, sulfocolaurate (N-2-ethyl laurate potassium
sulfoacetamide) and sodium lauryl sarcosinate. By "higher alkyl" is
meant, e.g., C.sub.6-30 alkyl. In particular embodiments, the
anionic surfactant (where present) is selected from sodium lauryl
sulfate and sodium ether lauryl sulfate. When present, the anionic
surfactant is present in an amount which is effective, e.g.,
>0.001% by weight of the formulation, but not at a concentration
which would be irritating to the oral tissue, e.g., 1%, and optimal
concentrations depend on the particular formulation and the
particular surfactant. In one embodiment, the anionic surfactant is
present at from 0.03% to 5% by weight, e.g., 1.5%.
[0157] In another embodiment, cationic surfactants useful in the
present invention can be broadly defined as derivatives of
aliphatic quaternary ammonium compounds having one long alkyl chain
containing 8 to 18 carbon atoms such as lauryl trimethylammonium
chloride, cetyl pyridinium chloride, cetyl trimethylammonium
bromide, di-isobutylphenoxyethyldimethylbenzylammonium chloride,
coconut alkyltrimethylammonium nitrite, cetyl pyridinium fluoride,
and mixtures thereof. Illustrative cationic surfactants are the
quaternary ammonium fluorides described in U.S. Pat. No. 3,535,421,
to Briner et al., herein incorporated by reference. Certain
cationic surfactants can also act as germicides in the
compositions.
[0158] Illustrative nonionic surfactants of Composition 1.0, et
seq., that can be used in the compositions of the invention can be
broadly defined as compounds produced by the condensation of
alkylene oxide groups (hydrophilic in nature) with an organic
hydrophobic compound which may be aliphatic or alkylaromatic in
nature. Examples of suitable nonionic surfactants include, but are
not limited to, the Pluronics, polyethylene oxide condensates of
alkyl phenols, products derived from the condensation of ethylene
oxide with the reaction product of propylene oxide and ethylene
diamine, ethylene oxide condensates of aliphatic alcohols, long
chain tertiary amine oxides, long chain tertiary phosphine oxides,
long chain dialkyl sulfoxides and mixtures of such materials. In a
particular embodiment, the composition of the invention comprises a
nonionic surfactant selected from poloxamers (e.g., poloxamer 407),
polysorbates (e.g., polysorbate 20), polyoxyl hydrogenated castor
oils (e.g., polyoxyl 40 hydrogenated castor oil), and mixtures
thereof.
[0159] Illustrative amphoteric surfactants of Composition 1.0, et
seq., that can be used in the compositions of the invention include
betaines (such as cocamidopropylbetaine), derivatives of aliphatic
secondary and tertiary amines in which the aliphatic radical can be
a straight or branched chain and wherein one of the aliphatic
substituents contains about 8-18 carbon atoms and one contains an
anionic water-solubilizing group (such as carboxylate, sulfonate,
sulfate, phosphate or phosphonate), and mixtures of such
materials.
[0160] The surfactant or mixtures of compatible surfactants can be
present in the compositions of the present invention (e.g.,
Composition 1.0 et seq) in 0.1% to 5%, in another embodiment 0.3%
to 3% and in another embodiment 0.5% to 2% by weight of the total
composition.
Flavoring Agents
[0161] The oral care compositions of the invention may also include
a flavoring agent. Flavoring agents which are used in the practice
of the present invention include, but are not limited to, essential
oils and various flavoring aldehydes, esters, alcohols, and similar
materials, as well as sweeteners such as sodium saccharin. Examples
of the essential oils include oils of spearmint, peppermint,
wintergreen, sassafras, clove, sage, eucalyptus, marjoram,
cinnamon, lemon, lime, grapefruit, and orange. Also useful are such
chemicals as menthol, carvone, and anethole. Certain embodiments
employ the oils of peppermint and spearmint.
[0162] The flavoring agent is incorporated in the oral composition
(e.g., Composition 1.0 et seq) at a concentration of 0.01 to 2% by
weight.
Chelating and Anti-Calculus Agents
[0163] The oral care compositions of the invention also may include
one or more chelating agents able to complex calcium found in the
cell walls of the bacteria. Binding of this calcium weakens the
bacterial cell wall and augments bacterial lysis.
[0164] Another group of agents suitable for use as chelating or
anti-calculus agents in the present invention are the soluble
pyrophosphates. The pyrophosphate salts used in the present
compositions can be any of the alkali metal pyrophosphate salts. In
certain embodiments, salts include tetra alkali metal
pyrophosphate, dialkali metal diacid pyrophosphate, trialkali metal
monoacid pyrophosphate and mixtures thereof, wherein the alkali
metals are sodium or potassium. The salts are useful in both their
hydrated and unhydrated forms. An effective amount of pyrophosphate
salt useful in the present composition is generally enough to
provide least 0.1 wt. % pyrophosphate ions, e.g., 0.1 to 3 wt 5,
e.g., 0.1 to 2 wt %, e.g., 0.1 to 1 wt %, e.g., 0.2 to 0.5 wt %.
The pyrophosphates also contribute to preservation of the
compositions by lowering water activity.
Polymers
[0165] The oral care compositions of the invention also optionally
include one or more polymers, such as polyethylene glycols,
polyvinyl methyl ether maleic acid copolymers, polysaccharides
(e.g., cellulose derivatives, for example carboxymethyl cellulose,
or polysaccharide gums, for example xanthan gum or carrageenan
gum). Acidic polymers, for example polyacrylate gels, may be
provided in the form of their free acids or partially or fully
neutralized water soluble alkali metal (e.g., potassium and sodium)
or ammonium salts. Certain embodiments include 1:4 to 4:1
copolymers of maleic anhydride or acid with another polymerizable
ethylenically unsaturated monomer, for example, methyl vinyl ether
(methoxyethylene) having a molecular weight (M.W.) of about 30,000
to about 1,000,000. These copolymers are available for example as
Gantrez AN 139 (M.W. 500,000), AN 1 19 (M.W. 250,000) and S-97
Pharmaceutical Grade (M.W. 70,000), of GAF Chemicals
Corporation.
[0166] Other operative polymers include those such as the 1:1
copolymers of maleic anhydride with ethyl acrylate, hydroxyethyl
methacrylate, N-vinyl-2-pyrollidone, or ethylene, the latter being
available for example as Monsanto EMA No. 1 103, M.W. 10,000 and
EMA Grade 61, and 1:1 copolymers of acrylic acid with methyl or
hydroxyethyl methacrylate, methyl or ethyl acrylate, isobutyl vinyl
ether or N-vinyl-2-pyrrolidone.
[0167] Suitable generally, are polymerized olefinically or
ethylenically unsaturated carboxylic acids containing an activated
carbon-to-carbon olefinic double bond and at least one carboxyl
group, that is, an acid containing an olefinic double bond which
readily functions in polymerization because of its presence in the
monomer molecule either in the alpha-beta position with respect to
a carboxyl group or as part of a terminal methylene grouping.
Illustrative of such acids are acrylic, methacrylic, ethacrylic,
alpha-chloroacrylic, crotonic, beta-acryloxy propionic, sorbic,
alpha-chlorsorbic, cinnamic, beta-styrylacrylic, muconic, itaconic,
citraconic, mesaconic, glutaconic, aconitic, alpha-phenylacrylic,
2-benzyl acrylic, 2-cyclohexylacrylic, angelic, umbellic, fumaric,
maleic acids and anhydrides. Other different olefinic monomers
copolymerizable with such carboxylic monomers include vinylacetate,
vinyl chloride, dimethyl maleate and the like. Copolymers contain
sufficient carboxylic salt groups for water-solubility.
[0168] A further class of polymeric agents includes a composition
containing homopolymers of substituted acrylamides and/or
homopolymers of unsaturated sulfonic acids and salts thereof, in
particular where polymers are based on unsaturated sulfonic acids
selected from acrylamidoalkane sulfonic acids such as 2-acrylamide
2 methylpropane sulfonic acid having a molecular weight of about
1,000 to about 2,000,000, described in U.S. Pat. No. 4,842,847,
Jun. 27, 1989 to Zahid, incorporated herein by reference.
[0169] Another useful class of polymeric agents includes polyamino
acids, particularly those containing proportions of anionic
surface-active amino acids such as aspartic acid, glutamic acid and
phosphoserine, as disclosed in U.S. Pat. No. 4,866,161 Sikes et
al., incorporated herein by reference.
[0170] In preparing oral care compositions, it is sometimes
necessary to add some thickening material to provide a desirable
consistency or to stabilize or enhance the performance of the
formulation. In certain embodiments, the thickening agents are
carboxyvinyl polymers, carrageenan, xanthan gum, hydroxyethyl
cellulose and water soluble salts of cellulose ethers such as
sodium carboxymethyl cellulose and sodium carboxymethyl
hydroxyethyl cellulose. Natural gums such as karaya, gum arabic,
and gum tragacanth can also be incorporated. Colloidal magnesium
aluminum silicate or finely divided silica can be used as component
of the thickening composition to further improve the composition's
texture. In certain embodiments, thickening agents in an amount of
about 0.5% to about 5.0% by weight of the total composition are
used.
Abrasives
[0171] Natural calcium carbonate is found in rocks such as chalk,
limestone, marble and travertine. It is also the principle
component of egg shells and the shells of mollusks. The natural
calcium carbonate abrasive of the invention is typically a finely
ground limestone which may optionally be refined or partially
refined to remove impurities. For use in the present invention, the
material has an average particle size of less than 10 microns,
e.g., 3-7 microns, e.g. about 5.5 microns. For example, a small
particle silica may have an average particle size (D50) of 2.5-4.5
microns. Because natural calcium carbonate may contain a high
proportion of relatively large particles of not carefully
controlled, which may unacceptably increase the abrasivity,
preferably no more than 0.01%, preferably no more than 0.004% by
weight of particles would not pass through a 325 mesh. The material
has strong crystal structure, and is thus much harder and more
abrasive than precipitated calcium carbonate. The tap density for
the natural calcium carbonate is for example between 1 and 1.5
g/cc, e.g., about 1.2 for example about 1.19 g/cc. There are
different polymorphs of natural calcium carbonate, e.g., calcite,
aragonite and vaterite, calcite being preferred for purposes of
this invention. An example of a commercially available product
suitable for use in the present invention includes Vicron.RTM.
25-11 FG from GMZ.
[0172] Precipitated calcium carbonate is generally made by
calcining limestone, to make calcium oxide (lime), which can then
be converted back to calcium carbonate by reaction with carbon
dioxide in water. Precipitated calcium carbonate has a different
crystal structure from natural calcium carbonate. It is generally
more friable and more porous, thus having lower abrasivity and
higher water absorption. For use in the present invention, the
particles are small, e.g., having an average particle size of 1-5
microns, and e.g., no more than 0.1%, preferably no more than 0.05%
by weight of particles which would not pass through a 325 mesh. The
particles may for example have a D50 of 3-6 microns, for example
3.8=4.9, e.g., about 4.3; a D50 of 1-4 microns, e.g. 2.2-2.6
microns, e.g., about 2.4 microns, and a D10 of 1-2 microns, e.g.,
1.2-1.4, e.g. about 1.3 microns. The particles have relatively high
water absorption, e.g., at least 25 g/100 g, e.g. 30-70 g/100 g.
Examples of commercially available products suitable for use in the
present invention include, for example, Carbolag.RTM. 15 Plus from
Lagos Industria Quimica.
[0173] In certain embodiments the invention may comprise additional
calcium-containing abrasives, for example calcium phosphate
abrasive, e.g., tricalcium phosphate (Ca.sub.3(PO.sub.4).sub.2),
hydroxyapatite (Ca.sub.10(PO.sub.4).sub.6(OH).sub.2), or dicalcium
phosphate dihydrate (CaHPO.sub.4.2H.sub.2O, also sometimes referred
to herein as DiCal) or calcium pyrophosphate, and/or silica
abrasives, sodium metaphosphate, potassium metaphosphate, aluminum
silicate, calcined alumina, bentonite or other siliceous materials,
or combinations thereof. Any silica suitable for oral care
compositions may be used, such as precipitated silicas or silica
gels. For example synthetic amorphous silica. Silica may also be
available as a thickening agent, e.g., particle silica. For
example, the silica can also be small particle silica (e.g.,
Sorbosil AC43 from PQ Corporation, Warrington, United Kingdom).
However the additional abrasives are preferably not present in a
type or amount so as to increase the RDA of the dentifrice to
levels which could damage sensitive teeth, e.g., greater than
130.
Water
[0174] Water is present in the oral compositions of the invention.
Water, employed in the preparation of commercial oral compositions
should be deionized and free of organic impurities. Water commonly
makes up the balance of the compositions and includes 5% to 45%,
e.g., 10% to 20%, e.g., 25-35%, by weight of the oral compositions.
This amount of water includes the free water which is added plus
that amount which is introduced with other materials such as with
sorbitol or silica or any components of the invention. The Karl
Fischer method is a one measure of calculating free water.
Humectants
[0175] Within certain embodiments of the oral compositions, it is
also desirable to incorporate a further humectant (e.g., in
addition to glycerin) to reduce evaporation and also contribute
towards preservation by lowering water activity. Certain humectants
can also impart desirable sweetness or flavor to the compositions.
The humectant, on a pure humectant basis, generally includes 15% to
70% in one embodiment or 30% to 65% in another embodiment by weight
of the composition.
[0176] Suitable humectants include edible polyhydric alcohols such
as glycerin, sorbitol, xylitol, propylene glycol as well as other
polyols and mixtures of these humectants. Mixtures of glycerine and
sorbitol may be used in certain embodiments as the humectant
component of the compositions herein (e.g., Composition 1.0 et
seq).
[0177] The present invention in its method aspect involves applying
to the oral cavity a safe and effective amount of the compositions
described herein.
[0178] The compositions and methods according to the invention
(e.g., Composition 1.0 et seq) can be incorporated into oral
compositions for the care of the mouth and teeth such as
toothpastes, transparent pastes, gels, mouth rinses, sprays and
chewing gum.
[0179] As used throughout, ranges are used as shorthand for
describing each and every value that is within the range. Any value
within the range can be selected as the terminus of the range. In
addition, all references cited herein are hereby incorporated by
reference in their entireties. In the event of a conflict in a
definition in the present disclosure and that of a cited reference,
the present disclosure controls. It is understood that when
formulations are described, they may be described in terms of their
ingredients, as is common in the art, notwithstanding that these
ingredients may react with one another in the actual formulation as
it is made, stored and used, and such products are intended to be
covered by the formulations described.
[0180] The following examples further describe and demonstrate
illustrative embodiments within the scope of the present invention.
The examples are given solely for illustration and are not to be
construed as limitations of this invention as many variations are
possible without departing from the spirit and scope thereof.
Various modifications of the invention in addition to those shown
and described herein should be apparent to those skilled in the art
and are intended to fall within the appended claims.
EXAMPLES
[0181] Aqueous solutions containing arginine and zinc salts were
created to carry out the following Examples. Solution 1 was
prepared by mixing L-arginine (0.375 g), zinc oxide (ZnO, 0.25 g),
and zinc citrate trihydrate (0.125 g) in deionized water (24.25
mL). These values correspond to the following percentages by mass:
1.5% L-arginine, 1% ZnO, 0.5% zinc citrate trihydrate. Additional
control solutions were prepared of each regent alone at equal
concentrations. Simple solution preparation is summarized in Table
1. Each solution was diluted to 25 g total mass with deionized
water.
TABLE-US-00001 TABLE 1 Preparation scheme of Solutions containing
Zinc Salts/Arginine and Controls Simple Solution Reagent Amount (g)
Mass Percent Zinc Oxide/Zinc L-arginine 0.375 1.5% Citrate/Arginine
ZnO 0.25 1.0% Zinc Citrate 0.125 0.5% Trihydrate Arginine
L-arginine 0.375 1.5% Zinc Oxide ZnO 0.250 1.0% Zinc Citrate Zinc
Citrate 0.125 0.5% Trihydrate
Example 1--Test for Buffering Effect of Zinc Oxide/Zinc
Citrate/Arginine Solution Following Acid Challenge with Cola
Beverage
[0182] Paraffin-stimulated whole saliva was collected from a
healthy subject. Each saliva sample was mixed by an appropriate
means. Immediately prior to analysis, the ex-vivo saliva samples
were pretreated with aliquots of Solution 1 to give a range of
active dilutions. A control sample containing untreated whole
saliva was also prepared for comparison. The dilutions were
prepared as in Table 2.
TABLE-US-00002 TABLE 2 Concentrations of zinc oxide/zinc
citrate/arginine treated saliva. Zinc Oxide/Zinc % Zinc Oxide/Zinc
Citrate/Arginine Citrate/Arginine Sample Stock (mL) Whole Saliva
(mL) Solution 1 0.00 4.000 0.000 2 0.100 3.900 0.025 3 0.250 3.750
0.0625 4 0.500 3.500 0.1250
[0183] The samples as described in Table 2 were tested for
buffering effect on the pH of saliva following acid challenge with
a cola beverage. Initial pH values of the treated samples were
obtained. A cola beverage (1 mL) was added to the saliva sample.
The resultant was mixed for 30 seconds at room temperature at the
conclusion of which the pH of the sample was recorded. This process
was repeated step-wise up to a total of 40 mL of cola. The results
are shown in FIG. 1. As shown, increasing concentrations of zinc
oxide/zinc citrate/arginine alkaline shifted the isoelectric point
of the saliva enhancing buffering capacity. Solutions having zinc
oxide/zinc citrate/arginine showed strong buffering effects at each
concentration measured. However, the results show that as the
concentration of zinc oxide/zinc citrate/arginine increases, the
buffering effect on the saliva also increases.
[0184] Similar tests were carried out to compare the buffering
effect against cola of control solutions containing L-arginine/zinc
oxide/zinc citrate as summarized below in Table 3.
TABLE-US-00003 TABLE 3 Concentrations of zinc oxide/zinc
citrate/arginine treated saliva in comparison with controls. %
Reagent in Sample Reagent (mL) Whole Saliva (mL) Solution 1 Zinc
Oxide/Zinc 3.750 0.0625 Citrate/arginine (.250) 2 L-Arginine (.250)
3.750 0.0625 3 Zinc Oxide/Zinc 3.750 0.0625 Citrate (.250) 4 Zinc
Oxide (.250) 3.750 0.0625 5 Zinc Citrate (.250) 3.750 0.0625
[0185] The titrations with the same cola beverage were repeated in
presence of saliva treated with the aforementioned zinc oxide/zinc
citrate/arginine controls (i.e., Samples 2-5 in Table 3). The
concentration of each reagent in control Samples 2-5 were held
constant in comparison to the 0.0625% zinc oxide/zinc
citrate/arginine simple solution. Therefore, direct comparison of
any effect could be made by each control solution to zinc
oxide/zinc citrate/arginine. As shown in FIG. 2, zinc oxide/zinc
citrate/arginine out performs all control solutions at equal
concentration of active agents. The zinc oxide/zinc
citrate/arginine solution showed much better ability to buffer the
acidic cola beverage than the control samples. The isoelectric
point of zinc oxide/zinc citrate/arginine is alkaline shifted more
than 5 mL in comparison to a zinc oxide/zinc citrate and a zinc
oxide solution. Zinc citrate and arginine conversely acid shifted
the isoelectric point in comparison to the untreated sample
providing no acid neutralization benefit.
Example 2--Test for Buffering Effect of Zinc Oxide/Zinc
Citrate/Arginine Solution Following Acid Challenge with Orange
Juice
[0186] Four solutions containing whole saliva and zinc oxide/zinc
citrate/arginine at varying proportions were prepared in accordance
with the methods laid out in Example 1 above. The solutions
contained the same concentrations as Samples 1-4 as defined in
Table 2. The samples were tested for buffering effect on the pH of
saliva following acid challenge with orange juice. Initial pH
values of the treated samples were obtained. Orange juice (0.1 mL)
was added to the saliva sample. The resultant was mixed for 30
seconds at room temperature at the conclusion of which the pH of
the sample was recorded. This process was repeated step-wise up to
a total of 3.0 mL of orange juice. After this point, orange juice
was added to the samples in an amount of 0.5 mL up to 5.0 mL. The
results are shown in FIG. 3. As shown, increasing concentrations of
zinc oxide/zinc citrate/arginine alkaline shifted the isoelectric
point of the saliva enhancing buffering capacity. Zinc oxide/zinc
citrate/arginine solutions showed strong buffering effects at each
concentration measured. However, the results show that as the
concentration of zinc oxide/zinc citrate/arginine increases, the
buffering effect on the saliva also increases, especially at
moderate amounts of orange juice (i.e., between 2 and 3 mL).
[0187] Similar tests as those in Example 1 were carried out to
compare the buffering effect against orange juice of solutions
containing L-arginine/zinc oxide/zinc citrate with control
solutions as summarized above in Table 3. The titrations with the
same orange juice were repeated in presence of saliva treated with
controls (i.e., Samples 2-5 in Table 3). The concentration of each
reagent in control Samples 2-5 were held constant in comparison to
the 0.0625% zinc oxide/zinc citrate/arginine simple solution. As
shown in FIG. 4, the zinc oxide/zinc citrate/arginine solution
showed an ability to buffer the acidic orange juice beverage better
than or on par with the control samples. The isoelectric point of
zinc oxide/zinc citrate/arginine is comparable to that of the zinc
oxide/zinc citrate and zinc oxide solution. Zinc citrate alone
showed no benefit in comparison the untreated control.
[0188] Taken together, the data clearly demonstrate the role of
zinc oxide/zinc citrate/arginine in enhancing the resistance of
saliva to acidic beverages. The data suggest the complex of
L-arginine/zinc oxide/zinc citrate, not the entities thereof
(arginine, zinc), are required for buffering effect.
Example 3--Test for Buffering Effect of Zinc Oxide/Zinc
Citrate/Arginine Solution Following Acid Challenge with
Hydrochloric Acid
[0189] Paraffin-stimulated whole saliva was collected from three
healthy subjects (Donors 1-3). Each saliva sample was mixed by
ordinary means in the art. Immediately prior to analysis, the
ex-vivo saliva samples were pretreated with aliquots of the simple
solutions to give a range of active dilutions (i.e., total
Zn.sup.2+ concentration of about 0-1500 ppm) including an untreated
control. The concentrations of actives (i.e., zinc oxide/zinc
citrate/arginine, L-arginine, zinc oxide, zinc citrate) were varied
between 0.0% to 50% across all samples, as shown in FIGS. 5-10.
[0190] An initial pH of the treated sample was obtained. Dilute
hydrochloric acid (HCl, 0.01 M, 6 mL) was added to each saliva
sample. The resultant was mixed for 20 minutes at room temperature.
The pH of the sample was recorded at the conclusion of the reaction
time. Zinc concentration in each sample was determined by ICP-AES.
The results are summarized in FIGS. 5-10.
[0191] FIGS. 5-7 show the superior acid buffering effects of even
small amounts of zinc oxide/zinc citrate/arginine over subsequent
control solutions. the results indicate that the combination of
zinc and L-arginine boosts the acid buffering capacity of saliva
over the L-arginine control. Surprisingly, this augmentation (up to
2 pH log units) is most evident in individuals with low salivary
buffering capacity (Donor #1 and Donor #3) at very low amounts of
treatment (<0.200 .mu.L). For example, FIGS. 5-7 each show that
the samples having 200 .mu.L or less zinc oxide/zinc
citrate/arginine showed much better buffering of the acid solutions
than each of the arginine, zinc oxide or zinc citrate solutions at
the same concentrations. The same figures show that only solutions
containing very high amounts of L-arginine (>500 .mu.L) were
able to match this effect. Zinc oxide provided some pH
stabilization in treated samples upon acid exposure. However, this
effect was quickly exhausted, not showing a dose response above
0.1% treatment. Furthermore, the overall pH of the saliva after
acid exposure was lower in saliva treated with ZnO than zinc
oxide/zinc citrate/arginine treated saliva. This leads to a larger
change in pH upon acid exposure in ZnO samples, decreasing benefits
on this active in comparison to zinc oxide/zinc citrate/arginine.
In all donors, zinc citrate provided little to no buffering effect
at all, dropping the pH of all treated samples below 4.0.
Example 4--Test for Buffering Effect of Zinc Oxide/Zinc
Citrate/Arginine Solution Following Sucrose Challenge
[0192] Paraffin-stimulated whole saliva was collected from three
healthy subjects (Donors A-C). Each saliva sample was mixed by
ordinary means in the art. Prior to analysis, the ex-vivo saliva
samples were pretreated with aliquots of the simple solutions to
give a range of active dilutions (i.e., total Zn.sup.2+
concentration of about 0-3000 ppm) including an untreated control
in order to test for buffering effect against sucrose challenge as
a function of zinc concentration. An initial pH of the treated
sample was obtained. A sucrose solution (5%, 1 mL) was added to
each saliva sample. The resultant was mixed for and then incubated
at 37.degree. C. and the pH was monitored at 2 hours, 4 hours, 6
hours, and overnight. Zinc concentration in each sample was
determined by ICP-AES.
[0193] Charts showing the pH of the saliva of each donor pre- and
post-sucrose challenge as a function of zinc (i.e., in zinc
oxide/zinc citrate/arginine solutions) concentration and time are
shown in FIGS. 8-10. The control sample of each donor saliva shows
a steady drop as a function of time consistent with unregulated
acid production by oral bacteria. However, upon adding zinc
oxide/zinc citrate/arginine, the effect on pH dropping is greatly
attenuated, even at smaller concentrations of zinc.
[0194] With specific reference to FIG. 8, solutions containing
concentrations of at least about 580 ppm Zn.sup.2+ showed a stable
buffering effect across the entire testing period. FIG. 10 shows
similar results for solutions containing concentrations of at least
about 478 ppm Zn.sup.2+. FIG. 9 shows that concentrations above 600
ppm Zn.sup.2+ (i.e., 1400 and 3000 ppm) exhibit stable saliva
buffering across the entire testing period, while the solution
containing 600 ppm Zn.sup.2+ showed a slight drop in buffering
effect after 6 hours. This buffering effect increases as the
concentration of zinc ions increase in the composition.
[0195] Further experiments were conducted to ensure that zinc
oxide/zinc citrate/arginine, not its constituent parts, was needed
to achieve the buffering capacity improvement described. The
solutions tested were prepared according to the specifications as
laid out in Table 3 above. As seen by FIG. 11, zinc oxide/zinc
citrate/arginine out performs its constituent controls in
maintaining a stable pH in response to bacterial acid
production.
[0196] As shown in FIGS. 12-14, pH of the saliva from donors A-C
were tested in sucrose challenged conditions as a function of
arginine concentration. It is only at relatively high
concentrations of arginine that any appreciable buffering effect is
observed (i.e., 250 ppm to 500 ppm arginine). In donor C, modest
buffering was observed with the 100 ppm arginine solution, but this
effect was not seen in donors A or B.
[0197] As shown in FIGS. 15-17, pH of the saliva from donors A-C
were tested in sucrose challenged conditions as a function of zinc
oxide/zinc citrate concentration. Buffering effects were clearly
observed over the untreated control of donor B as shown in FIG. 16,
but none of the zinc oxide/zinc citrate solutions in FIGS. 15-17
show a similar high level of buffering effect as the zinc
oxide/zinc citrate/arginine solution.
[0198] As shown in FIGS. 18-20, pH of the saliva from donors A-C
were tested in sucrose challenged conditions as a function of zinc
oxide concentration. Buffering effects were clearly observed over
the untreated control of each of the donors, but none of the zinc
oxide/zinc citrate solutions in FIGS. 18-20 show a similar high
level of buffering effect as the zinc oxide/zinc citrate/arginine
solution.
[0199] As shown in FIGS. 21-23, pH of the saliva from donors A-C
were tested in sucrose challenged conditions as a function of zinc
citrate concentration. Buffering effects were observed over the
untreated control of each of the donors, but none of the zinc
oxide/zinc citrate solutions in FIGS. 21-23 show a similar high
level of buffering effect as the zinc oxide/zinc citrate/arginine
solution.
[0200] Based on the above, it is apparent that zinc oxide/zinc
citrate/arginine is has an effect on saliva buffering capacity.
Without being bound by theory, the results indicate that zinc
oxide/zinc citrate/arginine can prevent the activities or
neutralize the products of acid-causing bacteria. Additionally, the
effect on pH could attributed to the antibacterial effects of zinc
oxide/zinc citrate/arginine.
Example 5--Representative Formulation
[0201] In one representative formulation, a dentifrice comprises
the following:
[0202] a. 1.0 wt. % zinc oxide
[0203] b. 0.5 wt. % zinc citrate
[0204] c. 1.5 wt. % L-arginine
[0205] d. 0.32 wt. % sodium fluoride; and
[0206] e. 35% wt. glycerin
Example 6--Representative Dentifrice Formulation
[0207] Representative Dentifrice Formulation:
TABLE-US-00004 Ingredient Formula 1 DEMINERALIZED WATER Q.S.
ABRASIVES 10%-20% 99.0%-101.0% GLYCERIN - 35 USP, EP VEG L-Arginine
1.5 AMPHOTERIC 1.0%-1.5% SURFACTANT NON-IONIC SURFACTANT
0.25%-0.75% POLYMERS 0.75%-1.5% ALKALI PHOSPHATE SALT 0.25%-0.75%
ZINC CITRATE 0.5 TRIHYDRATE WHITENING AGENT 0.25%-1.0% FLAVORING
AGENTS 1.5%-1.9% 85% SYRUPY PHOSPHORIC 0-0.35 ACID - FOOD GRADE
SODIUM FLUORIDE - USP, 0.32 EP SILICA - THICKENER 5%-7% ANIONIC
SURFACTANT 1%-3% ZINC OXIDE 1 PRESERVATIVE 0.4 Total Components
100
[0208] While the present invention has been described with
reference to embodiments, it will be understood by those skilled in
the art that various modifications and variations may be made
therein without departing from the scope of the present invention
as defined by the appended claims.
* * * * *